Adequate amino acid (AA) nutrition is essential for the health and well- being of humans and animals alike. Because AAs have no storage pool, the development of an essential AA deficiency can occur rapidly, particularly if a mild state of protein deficiency already exists. Since AA supplements have become fashionable, and may especially be used by dieters, AA imbalance should be recognized as a potential health hazard. Moreover, individuals with cancer cachexia, disorders of AA metabolism, and other metabolic aberrancies may also suffer AA disproportion. AA deficiencies have been shown to compromise growth and any bodily function that depends on protein synthesis, such wound healing. However, the growth reduction attributed to AA imbalance is actually secondary to the decreased food intake, an anorectic response to the AA deficiency. The long-term goal of the work in this laboratory is to understand how AA deficiency is recognized by the body, and how this deficiency is expressed in a readily available behavioral measure, food intake. Given the importance of AA nutrition, it is imperative that we gain a better understanding of the basic mechanisms by which AA imbalance affects feeding behavior. A well defined nutritional model using AA imbalanced (IMB) diets is available for these studies. The anterior prepyriform cortex (PPC) of the brain has been implicated as the prime candidate for the sensor of AA deficiency in the IMB-diet model. However, both blockade of the serotonin/3 receptor in the periphery nd vagotomy also modulate intake of IMB diets. Thus, interactions must occur among the several systems already known to play roles in the responses to IMB diets, as well as with other systems that may be revealed in the studies proposed here. PPC lesions that block the anorectic response to IMB diets usually are large enough to impinge on adjacent structures or fibers of passage to other brain regions, but it is not known what neural pathways are involved in making associations between the PPC and other implicated systems, such as the vagal system. Thus, we hypothesize that projections to one or more additional brain areas may be important in the response. Specific Aim 1 will be to identify the brain areas, in addition to the PPC, that are activated at the time of the initial anorectic response, using molecular probes for immediate early gene (IEG) that serve as markers for neural activity and specific lesions. Second, several specific neurochemical alterations have been found in previous studies, implicating neurotransmitters and other AA metabolites in the neurochemical responses to IMB diets, chiefly in the PPC. Specific Aim 2 will be to determine if neurochemical changes, similar to those already observed in the PPC, occur in the other areas defined in the IEG studies, and to define the receptors involved. Specific Aim 3 will address the interactions among these several systems, using neurochemical, neurosurgical and neuropharmacological techniques.